Supplementary Material for: Circulating Exosomal MicroRNA-21 as a Biomarker in Each Tumor Stage of Colorectal Cancer

<p><b><i>Objective:</i></b> We clarified the predictive and prognostic
value of circulating plasma exosomal microRNA-21 (miR-21) in each TNM
stage of colorectal cancer (CRC) patients. <b><i>Methods:</i></b> The
microRNA (miRNA) profiles of the plasma exosomes, primary tumor tissues,
and liver metastasis tissues from the same CRC patients were examined
using a microarray. For validation analysis, the plasma exosome samples
from 326 CRC patients were measured by TaqMan miRNA assays. <b><i>Results:</i></b>
In the miRNA microarray analyses, miR-21 showed the highest
upregulation in exosomes, primary tumor tissues, and liver metastasis
tissues. Significant correlations were demonstrated between exosomal
miR-21 and tissue miR-21 levels. As for the relationship to the
pathological condition, exosomal miR-21 showed a significant association
with liver metastasis and TNM stage. The overall survival (OS) rates
and disease-free survival (DFS) rates in high-exosomal-miR-21 patients
were significantly worse than those in low-miR-21 patients. Exosomal
miR-21 levels were an independent prognostic factor for OS and DFS in
CRC patients with TNM stage II or III, and for OS in patients with TNM
stage IV. <b><i>Conclusion:</i></b> Plasma exosomal miR-21 levels are a
useful biomarker for the prediction of recurrence and poor prognosis in
CRC patients with TNM stage II, III, or IV.</p>